Olumuyiwa Abiola Adejumobi

Chemopreventive effect of methanolic extract of Azadirachta indica on experimental Trypanosoma brucei induced oxidative stress in dogs

Introduction: The medicinal properties of Azadirachta indica have been harnessed for many years in the treatment of many diseases in both humans and animals. Materials and Methods: Twenty-five apparently healthy dogs weighing between 3 and 8 kg were randomly divided into five groups with five dogs in each group. Ameliorative effect of A. indica on erythrocyte antioxidant status and markers of oxidative stress were assessed. Liver and kidney function tests were also performed. Results: Pre-treatment with methanolic extract of Azadirachta indica (MEAI) at different doses did not significantly alter the values of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activity in Trypanosoma brucei infection. Although, serum creatinine significantly (P < 0.05) decreased with pre-treatment with 50 mg/kg A. indica, after 2 weeks of T. brucei infection. However, the reduced glutathione (GSH) content of the erythrocyte increased significantly in animals pre-treated with 50 mg/kg and 200 mg/kg of A. indica respectively. Markers of oxidative stress such as malondialdehyde and hydrogen peroxide generated were higher in animals infected with T. brucei with no significant (P >0.05) difference compared to the values obtained in pre-treated animals. Pre-treatment with 100 mg/kg and 200 mg/kg of A. indica significantly (P < 0.05) decreased serum myeloperoxidase activity at 2 weeks post-infection with T. brucei. Conclusion: From this study, MEAI showed significant ability to attenuate oxidative stress and inflammation during experimental T. brucei infection.

Effect of arsenic acid withdrawal on hepatotoxicity and disruption of erythrocyte antioxidant defense system

Graphical abstract

Ameliorative effect of gallic acid on doxorubicin-induced cardiac dysfunction in rats

Abstract Background: The use of doxorubicin (DOX) as an antineoplastic agent has been greatly limited because of the myriad of toxic sequelae associated with it. The aim of this study was to assess the protective effects of gallic acid (GA) on DOX-induced cardiac toxicity in rats. Methods: Sixty male rats (Wistar strain) were used in this study. They were divided into six groups (A–F) each containing 10 animals. Group A was the control. Rats in Groups B, C, and D were treated with DOX at the dosage of 15 mg/kg body weight i.p. Prior to this treatment, rats in Groups C and D had been treated orally with GA for 7 days at the dosage of 60 and 120 mg/kg, respectively. Animals from Groups E and F received only 60 and 120 mg/kg GA, respectively, which were administered orally for 7 days. Results: The exposure of rats to DOX led to a significant (p<0.05) decrease in the cardiac antioxidant defence system and elevation of creatine kinase myocardial band and lactate dehydrogenase. The electrocardiography results showed a significant decrease in heart rate, QRS, and QT-segment prolongation. GA alone improved the antioxidant defence system. Conclusions: The GA pretreatment significantly alleviated GA-associated ECG abnormalities, restored the antioxidant status and prevented cardiac damage.

Preconditioning with Azadirachta indica ameliorates cardiorenal dysfunction through reduction in oxidative stress and extracellular signal regulated protein kinase signalling.

Background Azadirachta indica is widely distributed in Africa, Asia and other tropical parts of the world. A. indica (AI) is traditionally used for the treatment of several conditions including cancer, hypertension, heart diseases and skin disorders. Intestinal ischaemia-reperfusion is a common pathway for many diseases and may lead to multiple organ dysfunction syndrome and death. Objective In this study, we investigated the ameliorative effects of AI on intestinal ischaemia-reperfusion injury-induced cardiorenal dysfunction. Materials and methods Sixty rats were divided into 6 groups; each containing 10. Corn oil was orally administered to group A (control) rats for 7 days without intestinal ischaemia-reperfusion injury. Group B underwent intestinal ischaemia-reperfusion injury (IIRI) without any pre-treatment. Groups C, D, E and F were pre-treated orally for 7 days with 100 mg/kg AI (100 and (200 mg/kg) vitamin C (100 and 200 mg/kg) respectively and thereafter underwent IIRI on the 8th day. Results The cardiac and renal hydrogen peroxide increased significantly whereas serum xanthine oxidase and myeloperoxidase levels were significantly elevated (p < 0.05) in IIRI only when compared to the control. The cardiac and renal reduced glutathione, glutathione peroxidase, protein thiol, non-protein thiol and serum nitric oxide (NO) decreased (p < 0.05) significantly following IIRI. Immunohistochemical evaluation of cardiac and renal tissues showed reduced expressions of the extracellular signal regulated kinase (ERK1/2) in rats with IIRI only. However, pre-treatment with A. indica and vitamin C significantly reduced markers of oxidative stress and inflammation together with improvement in antioxidant status. Also, reduced serum NO level was normalised in rats pre-treated with A. indica and vitamin C with concomitant higher expressions of cardiac and renal ERK1/2. Conclusions Together, A. indica and vitamin C prevented IRI-induced cardiorenal dysfunction via reduction in oxidative stress, improvement in antioxidant defence system and increase in the ERK1/2 expressions. Therefore, A. indica can be a useful chemopreventive agent in the prevention and treatment of conditions associated with intestinal ischaemia-reperfusion injury.

Ameliorative effect of Azadirachta indica on sodium fluoride-induced hypertension through improvement of antioxidant defence system and upregulation of extracellular signal regulated kinase 1/2 signaling

Abstract Background: Toxicities due to fluoride exposure from natural and industrial sources occur commonly in man and animals with severe consequences ranging from mild cardiac derangements to sudden death. In this study, we investigated the protective effects of the methanol extract of Azadirachta indica (AI) against sodium fluoride (NaF)-induced hypertension and genotoxicity in rats. Methods: Sixty rats were divided into six groups of ten rats each as follows: Group A, the control group received distilled water; Group B rats were administered NaF at 600 ppm in drinking water; Groups C and D rats were pre-treated with the methanol extract of AI and thereafter administered NaF at 600 ppm in drinking water for 7 consecutive days; Groups E and F rats were co-administered with AI and NaF. Results: The administration of NaF caused significant (p<0.05) increases in the blood pressure, markers of oxidative stress, serum myeloperoxidase, xanthine oxidase values in NaF-alone treated rats, compared with the control. Significant (p<0.05) decreases were observed in cardiac and renal antioxidant defence system in rats administered NaF alone compared with the control group. NaF treatment also resulted in a reduction in the expressions of extracellular signal-regulated kinase (ERK) 1/2 in cardiac and renal tissues of NaF-treated rats. Moreover, NaF treatment elicited an increase in the frequency of micronucleated polychromatic erythrocytes when compared with the control group. Conclusions: This study shows the protective effect of AI on NaF-induced hypertension and genotoxicity through antioxidant and ERK 1/2 signaling in rats.

Protective Effect of Azadirachta indica and Vitamin E Against Arsenic Acid-Induced Genotoxicity and Apoptosis in Rats

ABSTRACT Sodium arsenite (NaAsO2) is one of the major environmental toxicants with severe toxicological consequences in some developing and developed countries. Rats in Group A received normal saline. Genotoxicity and apoptosis were induced by single intraperitoneal injection of 10 mg/kg sodium arsenite to rats in Groups B–F. Rats in Groups C and D had earlier been pretreated with Azadirachta indica (100 and 200 mg/kg) or E and F with vitamin E (50 and 100 mg/kg), respectively. Markers of oxidative stress, inflammation, hepatic damage, genotoxicity, and apoptosis were assessed. Pretreatment of rats with either Azadirachta indica or vitamin E led to a significant (p <.05) increase in the activities of glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) in the liver compared to the group that received NaAsO2 alone. Markers of oxidative stress and inflammation, malondialdehyde (MDA), hydrogen peroxide (H2O2) generation, nitric oxide (NO), and myeloperoxidase (MPO), were significantly (p <.05) lowered in rats pretreated with Azadirachta indica or vitamin E. The frequency of micronucleated polychromatic erythrocytes (MNPCEs) and expression of caspase-3 were significantly (p <.05) reduced in rats pretreated with either Azadirachta indica or vitamin E compared to rats intoxicated with arsenite. Histopathology of the liver showed areas of infiltration of inflammatory cells with deaths of numerous hepatocytes in NaAsO2-intoxicated rats, and these were reversed by Azadirachta indica. Together, we report for the first time the genoprotective and antiapoptotic effect of Azadirachta indica by a significant reduction in the frequency of micronuclei-induced apoptosis and oxidative stress by arsenic intoxication.

Ameliorative effect of Rutin on sodium fluoride-induced hypertension through modulation of Kim-1/NF-κB/Nrf2 signaling pathway in rats

Sodium fluoride is one of the neglected environmental contaminants. Inorganic fluorides in the environment are found in the air, water, and land. In the study, forty‐male Wistar albino rats were randomly divided into four groups with 10 rats in a group. Group A was the control group which was given normal saline, Group B was exposed to 300 ppm of NaF in drinking water, while Groups C and D received NaF along Rutin (100 mg/kg and 200 mg/kg) orally daily for a week. Administration of NaF alone led to significant increases in blood pressure, and deceased serum nitric oxide. Immunohistochemistry revealed higher expressions of kidney injury molecule I (Kim‐1), nuclear factor kappa beta (NF‐κB), and down regulation of nuclear factor erythroid 2‐related factor 2 (Nrf2) in rats administered NaF. Rutin co‐treatment with NaF normalized blood pressure, lowered Kim‐1 and NF‐κB expressions, and improved nitric oxide bioavailability.

Correction: Antihypertensive Effect of Polyphenol-Rich Fraction of Azadirachta indica on Nω-Nitro-L-Arginine Methyl Ester-Induced Hypertension and Cardiorenal Dysfunction

Azadirachta indica (AI) is a medicinal plant with reported antioxidant and cardio-protective properties. The use of plant-based polyphenols has become greatly increased in the last one decade. The present study investigated the protective effect of the polyphenol-rich fraction (PRF) of the methanol-extract of Azadirachta indica against Nω-Nitro-L-Arginine Methyl Ester (L-NAME) induced hypertension and cardiorenal dysfunction in rats. Fifty (50) Wistar albino rats were grouped into five groups. Group A, the control, was administered potable water. Groups B-E received orally, 40 mg/kg of L-NAME only, 40 mg/kg of L-NAME and 100 mg/kg of AI extract, 40 mg/kg of L-NAME and 200 mg/kg of AI extract, and 40 mg/kg of L-NAME and 25 mg/kg of captopril, respectively for 21 days. The results of the present study revealed that L-NAME administration led to a significant increase in systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. Markers of oxidative stress (malondialdehyde,protein carbonyl) increased significantly while there was reduction in reduced glutathione level, activities of superoxide dismutase, glutathione peroxidase and glutathione-S-transferase as well nitric oxide bioavailability. Immunohistochemistry revealed higher expressions of nuclear factor kappa beta (NF-kB) and kidney injury molecule 1(Kim-1) and lower expressions of nuclear factor erythroid 2–related factor 2 (Nrf2) in hypertensive rats. Our results indicated that with PRF of AI restored high blood pressure, reduced markers of oxidative stress, normalized serum NO bioavailability and increased the expressions of Nrf2. Hence, PRF of Azadirachta indica could be used for the treatment of hypertension.

Reduction in nitric oxide bioavailability shifts serum lipid content towards atherogenic lipoprotein in rats

Nitric oxide (NO) is major endothelial relaxing factor and reduction in its bioavailabilty has been linked to hypertension. Furthermore, high lipid content is a strong risk factor predisposing to cardiovascular diseases. The principal focus of this study was to investigate the effect of blockade of nitric oxide synthase (NOS) on serum lipid content in rats. Male Wistar rats (150-170 g, n = 15) were randomly divided into two groups designated control (n = 5), and L-Name group (n = 10) and were gavage with distilled water and 60 mg/kg of L-NAME respectively daily for three weeks. After 3 weeks, the L-NAME group was sub-divided into two sub-groups (n = 5 each): L-NAME (60 mg/kg of L-NAME), and L-NAME plus ramipril (LR) (60 mg/kg of L-NAME plus 20 mg/kg of ramipril) and were treated daily for another three weeks. The blood pressure (BP) of the conscious rats was measured by tail-cuff method at the onset, at the third and at the sixth weeks of the experiment; while serum lipid contents and NO were measured at the third and sixth weeks. At the end of the experiment blood sample was drawn by ocular puncture for evaluation of lipid profile and NO, and the animals were later euthanized by overdose of anaesthesia. Data were analyzed using ANOVA at p < 0.05. There was a significant increase in BP, triglyceride, total cholesterol, low density lipoprotein-cholesterol, and atherogenic indices in L-NAME group compared to the control and LR group (p < 0.05); NO and high density lipoprotein-cholesterol was significant lower in the L-NAME group compared to control and LR (p < 0.05). In conclusion, reduction in NO bioavailability alters lipid metabolism, which was rectified by ramipril.

Quercetin attenuates hypertension induced by sodium fluoride via reduction in oxidative stress and modulation of HSP 70/ERK/PPARγ signaling pathways: Quercetin attenuates hypertension induced by sodium fluoride

Hypertension is one of the silent killers in the world with high mortality and morbidity. The exposure of humans and animals to fluoride and/or fluoride containing compounds is almost inevitable. This study investigated the modulatory effects of quercetin on sodium fluoride (NaF)-induced hypertension and cardiovascular complications. Forty male rats were randomly separated into four groups (n =10). Group A animals served as the control, rats in Group B were exposed to 300 ppm of NaF, Groups C and D animals were exposed to 300 ppm of NaF along with quercetin orally at 50 mg/kg and 100 mg/kg orally by gavage, while NaF was administered in drinking water, respectively, for a week. Administration of NaF caused severe hypertension as indicated with significant increases in the systolic, diastolic, and mean arterial blood pressure, together with prolonged ventricular depolarization (QRS) and the time between the start of the Q wave and the end of the T wave in the hearts electrical cycle (QT) intervals when compared with controls. NaF significantly decreased the activities of antioxidant enzymes, caused increase in markers of oxidative stress and renal damage when compared with controls. Immunohistochemical staining revealed lower expressions of Hsp70, ERK, and PPARγ in the heart, kidney, and aorta of rats-administered NaF relative to the controls. Together, quercetin co-treatment with NaF restored blood pressure, normalized QRS interval, and improved antioxidant defense system.